Bone detects may be caused by a number of different factors including, but not limited to, trauma, pathological disease or surgical intervention. Because bone provides both stability and protection to an organism, these detects can be problematic. In order to address these defects, compositions and carriers that contain both natural and synthetic materials have been developed. These compositions and carriers may, depending upon the materials contained within them, be used to repair tissues and to impart desirable biological and/or mechanical properties to the bone defect.
Compositions and carriers may contain materials that are found in mammalian bone tissue which contains one or more proteinaceous materials, active during growth and natural bone healing that can induce a developmental cascade of cellular events resulting in bone formation. Various developmental factors are present in bone. These include bone morphogenetic proteins (BMPs), other bone inductive proteins, bone growth factors, or osteogenic proteins.
BMPs are a class of proteins in the superfamily of transforming growth factor-beta (TGF-β) thought to have osteoinductive or growth-promoting activities on endogenous bone tissue, or function as pro-collagen precursors. Because of these qualities, BMP has been commonly used in conjunction with compositions and carriers (e.g., bone scaffolds and matrices) for bone formation at bone defect sites and bone void sites. For example, bone morphogenetic protein 2 (BMP-2) is commonly placed on a collagen carrier and implanted at a target tissue site. Once the collagen carrier is implanted, it becomes a stationary matrix and the BMP-2 would draw osteoblasts and osteoclasts into the matrix in order to form new bone for fusion. The matrix containing the BMP-2 will promote the migration, proliferation and differentiation of bone cells for bone regeneration.
Generally, it was assumed that BMP-2 required delivery on a stationary matrix in order for it to be effective. It was thought that for the BMP-2 to remain biologically active, a stationary matrix was needed to preserve the conformational integrity of at least a core sequence of the protein's amino acids while at the same time protecting the protein's multiple functional groups from degradation. A matrix was believed to protect unreleased protein from direct contact with bodily fluid which could degrade the protein.
However, in situations where a stationary matrix is not wanted, such as bone defects in a high area of circulation where the matrix can dislodge and form an unwanted thrombosis, an injectable solution would be more desirable. Further, there may be difficulty when injecting a matrix percutaneously into a target bone defect site due to its size, new bone forming solutions are needed. Therefore, new methods and compositions to deliver BMP to a bone defect would be beneficial. Further, new dosing regimens that allow easy administration to a bone defect that avoids the use of a stationary matrix would also be desirable.